Solving the riddle of codon usage preferences: a test for translational selection

Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model

The Arches Cluster: Extended Structure and Tidal Radius

At a projected distance of ~26 pc from Sgr A*, the Arches cluster provides insight to star formation in the extreme Galactic Center (GC) environment. Despite its importance, many key properties such as the cluster's internal structure and orbital history are not well known. We present an astrometric and photometric study of the outer region of the Arches cluster (R > 6.25") using HST WFC3IR. Using proper motions we calculate membership probabilities for stars down to F153M = 20 mag (~2.5 M_sun) over a 120" x 120" field of view, an area 144 times larger than previous astrometric studies of the cluster. We construct the radial profile of the Arches to a radius of 75" (~3 pc at 8 kpc), which can be well described by a single power law. From this profile we place a 3-sigma lower limit of 2.8 pc on the observed tidal radius, which is larger than the predicted tidal radius (1 - 2.5 pc). Evidence of mass segregation is observed throughout the cluster and no tidal tail structures are apparent along the orbital path. The absence of breaks in the profile suggests that the Arches has not likely experienced its closest approach to the GC between ~0.2 - 1 Myr ago. If accurate, this constraint indicates that the cluster is on a prograde orbit and is located front of the sky plane that intersects Sgr A*. However, further simulations of clusters in the GC potential are required to interpret the observed profile with more confidence.Comment: 24 pages (17-page main text, 7-page appendix), 24 figures, accepted to Ap

The Quintuplet Cluster: Extended Structure and Tidal Radius

The Quintuplet star cluster is one of only three known young ($<10$ Myr) massive (M $>10^4$ M$_\odot$) clusters within $\sim100$ pc of the Galactic Center. In order to explore star cluster formation and evolution in this extreme environment, we analyze the Quintuplet's dynamical structure. Using the HST WFC3-IR instrument, we take astrometric and photometric observations of the Quintuplet covering a $120''\times120''$ field-of-view, which is $19$ times larger than those of previous proper motion studies of the Quintuplet. We generate a catalog of the Quintuplet region with multi-band, near-infrared photometry, proper motions, and cluster membership probabilities for $10,543$ stars. We present the radial density profile of $715$ candidate Quintuplet cluster members with $M\gtrsim4.7$ M$_\odot$ out to $3.2$ pc from the cluster center. A $3\sigma$ lower limit of $3$ pc is placed on the tidal radius, indicating the lack of a tidal truncation within this radius range. Only weak evidence for mass segregation is found, in contrast to the strong mass segregation found in the Arches cluster, a second and slightly younger massive cluster near the Galactic Center. It is possible that tidal stripping hampers a mass segregation signature, though we find no evidence of spatial asymmetry. Assuming that the Arches and Quintuplet formed with comparable extent, our measurement of the Quintuplet's comparatively large core radius of $0.62^{+0.10}_{-0.10}$ pc provides strong empirical evidence that young massive clusters in the Galactic Center dissolve on a several Myr timescale.Comment: 25 pages (21-page main text, 4-page appendix), 18 figures, submitted to Ap

A framework to support risk assessment in hospitals

In healthcare, risk assessment is used alongside a number of reactive risk management approaches to ensure the quality and safety of the care delivered. However, problems have been identified regarding its current application in hospitals, despite the considerable efforts made. In this paper, we present a framework that aims to address these current challenges and to guide staff working in healthcare settings in undertaking an effective risk assessment in hospitals. We report on the design of this framework, where we used a V developmental model, in conjunction with mixed methods, including interviews, document analysis and group discussions. The framework consists of a risk assessment model that depicts the main risk assessment steps; risk assessment explanation cards that provide prompts to help apply each step; and a risk assessment form that helps to systematise the risk assessment and document the findings. We also report on the evaluation of the framework, which shows promising results. While the framework was recommended for use in practice, it was also suggested that it would be helpful as a training tool. With its use in risk assessment, we anticipate that risk assessments would lead to more effective decisions being made, and, thus, to more appropriate actions being taken to minimise risks. Consequently, the quality and safety of care delivered would be improved.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of Englan

Design for Patient Safety: A Systems-based Risk Identification Framework

Current risk identification practices applied to patient safety in healthcare are insufficient. The situation can be improved, however, by studying systems approaches broadly and successfully utilised in other safety-critical industries, such as aviation and chemical industries. To illustrate this, this paper first investigates current risk identification practices in the healthcare field, and then examines the potential of systems approaches. A systems-based approach, called the Risk Identification Framework (RID Framework), is then developed to enhance improvement in risk identification. Demonstrating the strengths of using multiple inputs and methods, the RID Framework helps to facilitate the proactive identification of new risks. In this study, the potential value of the RID Framework is discussed by examining its application and evaluation, as conducted in a real-world healthcare setting. Both the application and evaluation of the RID Framework indicate positive results, as well as the need for further research.This research was partly funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of England, at Cambridgeshire and Peterborough National Health Service Foundation Trust